An investigational new drug for pulmonary hypertension may improve
the quality of life for thousands of patients with lupus, scleroderma,
and other associated connective tissue diseases, according to research
presented at the American College of Rheumatology Annual Scientific
Meeting in San Antonio, Texas.

Lupus, scleroderma and related connective tissue diseases are chronic
inflammatory autoimmune diseases that can damage the blood vessels
of the lung and other organs. Pulmonary hypertension, which is high
blood pressure in the lungs, occurs occasionally in people with
lupus. If severe, this condition can be life-threatening, and there
tends to be little chance for improvement. Patients with pulmonary
hypertension have elevated levels of endothelin, a powerful blood
vessel constrictor, in their plasma and lung tissue.

Researchers conducted a multicenter, randomized, double-blind,
placebo-controlled trial of sitaxsentan, a once-daily oral endothelin
receptor antagonist which blocks the action of endothelin on blood
vessels to determine whether it could improve the ability of pulmonary
hypertension patients to exercise without difficulty. This 12-week
trial involved 178 patients with pulmonary hypertension, 42 of whom
had pulmonary hypertension related to a connective tissue disease.
Patients received either 100mg or 300 mg of sitaxsentan, or placebo,
for 12 weeks. All patients participated in the 6-minute walk test,
the standard test for treatments for pulmonary hypertension that
measures how far an individual can walk in six minutes, before the
treatment began and again at the end of the 12-week trial. Researchers
found that patients with pulmonary hypertension related to connective
tissue disease who were taking either the 100mg or 300mg dosage
significantly improved their walking distance as compared to those
taking placebo (whose time actually worsened).

"Sitaxsentan was shown to significantly improve six-minute
walk distance, as well as hemodynamics such as cardiac index and
pulmonary vascular resistance for patients with pulmonary hypertension
related to connective tissue disease," said lead investigator
Vallerie McLaughlin, MD, University of Michigan Hospital, Ann Arbor,
Michigan. "The first therapy shown to improve key efficacy
variables in this population was epoprostenol, a prostacyclin therapy
that requires a central catheter and continuous intravenous infusion
that is often difficult for patients to tolerate. Thus, the ability
of an oral, once daily therapy such as sitaxsentan sodium to improve
key efficacy variables represents an important treatment advance."